Our goal is to use a simple murine model to elucidate the primary cause of an inherited form of epilepsy. Epilepsy is a significant health problem in humans - the second most common human neurological affliction affecting about 1% of the human population. However, the genetic heterogeneity in many humans epilepsies has hindered attempts to understand the modes of inheritance of epilepsies in human, and the precise causes and pathogenetic mechanisms of epilepsy remain obscure. Animal models have been used extensively for assessing drug treatments, but the comprehensive analysis of a genetically inherited animal model for epilepsy has yet to be described. Stargazer, a murine model with spontaneous seizures, is a single autosomal gene mutant and fulfills the requirements of a simple model for idiopathic epilepsy. We have fine- mapped the stargazer (stg) mutation and we propose to prepare an overlapping array of yeast artificial chromosomes from a close genetic marker to the stg locus. We will then isolate genomic DNA, cDNA and exon clones from the YAC encompassing the stg locus and use these clones to identify and isolate the stg gene from the parent and mutant mice for sequence and functional analysis. Thus we will be able to determine the nature of the primary defect and secondary consequences of epilepsy in the stargazer mutant, and apply our understanding of this relatively simple model to other more complex inherited epileptic disorders.